C-reactive protein (CRP) has long been known to appear in the blood during reactions of inflammation and tissue destruction. However, the role that it plays in these reactions is not yet clear. While structurally distinct from immunoglobulins, it shares with them the ability to initiate precipitation, agglutination, and complement consumption reactions and has a similar amino acid composition. We now have observed CRP to be a potent activator of the complement system when interacting with polycationic substrates, to selectively combine with T-lymphocytes and influence their functions, and to interfere with platelet aggregation reactions. It seems not unlikely that it has critical and pervasive functions in the body economy. Our major objective is to define the biological role of CRP in reactions of inflammation, repair, tissue destruction and resistance, with emphasis on its interrelationships with the host defense mechanisms, and to help elucidate ways in which CRP responses can be interpreted or manipulated to clinical advantage. We propose to define aspects of the structure of human CRP which relate to its functional analogy to immunoglobulin; define the range of substrates with which it interacts; delineate its interrelationships with the major components of the immune apparatus including complement, lymphocytes, platelets, granulocytes, and macrophages; define its interactions with normal and modified endogenous and exogenous membranes; define its metabolism and the factors which govern it; investigate its appearance and reactivity in the phylogenetic and ontogenetic perspectives; and study its role in human disease processes and its interactions in experimental animals in vivo. We hope in these ways to contribute to an understanding of the functions and role of CRP in health and disease, and to learn more about the adaptive processes involved in the inflammatory response generally.